When the United States implemented civilian and military smallpox vaccination programs in 2003, the National Smallpox Vaccine in Pregnancy Registry was established to better evaluate outcomes after the inadvertent vaccination of pregnant women. Women were referred to the registry by vaccine administrators, health care providers, or state health departments or through self-referral. Registry professionals actively follow up with all enrolled women and collect data on pregnancy, birth, and infant health outcomes. As of September 2006, pregnancy outcome data were available from 376 women. Most (77%) were vaccinated near the time of conception, before results of a standard pregnancy test would have been positive. To date, outcome evaluations have not revealed higher-than-expected rates of pregnancy loss (11.9%), preterm birth (10.7%), or birth defects (2.8%), compared with those in healthy referent populations. No cases of fetal vaccinia have been identified. The Smallpox Vaccine in Pregnancy Registry continues to actively enroll women and follow infant and early-childhood health outcomes.